scholarly journals piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association With Luminal Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Xin Ding ◽  
Ya Li ◽  
Jinhui Lü ◽  
Qian Zhao ◽  
Yuefan Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Stem Cell ◽  
Cancer Cells ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
Dna Methyltransferases ◽  
Luminal Breast Cancer ◽  
Stem Cell Markers ◽  
Luminal Subtype

Cancer stem cells (CSCs) are believed to be the main source of cancer relapse and metastasis. PIWI-interacting small non-coding RNAs (piRNAs) have been recently recognized to be relevant to cancer biology. Whether and how piRNAs regulate human CSCs remain unknown. Herein, upregulation of piR-823 was identified in tested luminal breast cancer cells, especially in the luminal subtype of breast CSCs. Enforced expression or targeted knockdown of piR-823 demonstrated its oncogenic function in regulating cell proliferation and colony formation in MCF-7 and T-47D breast cancer cells. In addition, piR-823 induced ALDH (+) breast CSC subpopulation promoted the expression of stem cell markers including OCT4, SOX2, KLF4, NANOG, and hTERT, and increased mammosphere formation. Tail vein injection of magnetic nanoparticles carrying anti-piR-823 into the mammary gland of tumor-burdened mice significantly inhibited tumor growth in vivo. DNA methyltransferases (DNMTs) including DNMT1, DNMT3A, and DNMT3B were demonstrated to be the downstream genes of piR-823, which regulate gene expression by maintaining DNA methylation. piR-823 increased the expression of DNMTs, promoted DNA methylation of gene adenomatous polyposis coli (APC), thereby activating Wnt signaling and inducing cancer cell stemness in the luminal subtype of breast cancer cells. The current study not only revealed a novel mechanism through which piRNAs contribute to tumorigenesis in breast cancer by regulating CSCs, but also provided a therapeutic strategy using non-coding genomes in the suppression of human breast cancer.

scholarly journals Breast cancer cells expressing stem cell markers CD44+ CD24lo are eliminated by Numb-1 peptide-activated T cells

2008 ◽  
Vol 58 (8) ◽  
pp. 1185-1194 ◽  
Author(s):  
Takashi Mine ◽  
Satoko Matsueda ◽  
Yufeng Li ◽  
Hiroshi Tokumitsu ◽  
Hui Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Stem Cell Markers ◽  
Activated T Cells ◽  
Cell Markers

scholarly journals Breast Cancer Stem Cells Survive Periods of Farnesyl-Transferase Inhibitor-Induced Dormancy by Undergoing Autophagy

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Moumita Chaterjee ◽  
Kenneth L. van Golen
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Potential ◽  
Stem Cell Markers ◽  
Farnesyl Transferase ◽  
Differentiated Cells ◽  
A Cell ◽  
Cluster Of Differentiation

A cancer stem cell has been defined as a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. These tumor-forming cells could hypothetically originate from stem, progenitor, or differentiated cells. Previously, we have shown that breast cancer cells with low metastatic potential can be induced into a reversible state of dormancy by farnesyl transferase inhibitors (FTIs). Dormancy was induced by changes in RhoA and RhoC GTPases. Specifically, RhoA was found to be hypoactivated while RhoC was hyperactivated. In the current study we demonstrate that these dormant cells also express certain known stem cell markers such as aldehyde dehydrogenase I (ALDHI) and cluster of differentiation 44 (CD44). We also show that autophagy markers Atg5, Atg12, and LC3-B are expressed in these dormant stem cell-like breast cancer cells. Inhibiting autophagy by inhibitor 3-methyladenine (3-MA) blocked the process of autophagy reversing the dormant phenotype. Further, we show that c-jun NH2 terminal kinase (JNK/SAPK) is upregulated in these dormant stem cell-like breast cancer cells and is responsible for increasing autophagy.

scholarly journals Endocrine Therapy of Estrogen Receptor-Positive Breast Cancer Cells: Early Differential Effects on Stem Cell Markers

2017 ◽  
Vol 7 ◽  
Author(s):  
Euphemia Y. Leung ◽  
Marjan E. Askarian-Amiri ◽  
Debina Sarkar ◽  
Carole Ferraro-Peyret ◽  
Wayne R. Joseph ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Stem Cell ◽  
Cancer Cells ◽  
Endocrine Therapy ◽  
Breast Cancer Cells ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

scholarly journals CRIPTO antagonist ALK4L75A-Fc inhibits breast cancer cell plasticity and adaptation to stress

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Ozlen Balcioglu ◽  
Richard E. Heinz ◽  
David W. Freeman ◽  
Brooke L. Gates ◽  
Berhane M. Hagos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Nutrient Deprivation ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Cancer Stem Cell Markers

Abstract Background CRIPTO is a multi-functional signaling protein that promotes stemness and oncogenesis. We previously developed a CRIPTO antagonist, ALK4L75A-Fc, and showed that it causes loss of the stem cell phenotype in normal mammary epithelia suggesting it may similarly inhibit CRIPTO-dependent plasticity in breast cancer cells. Methods We focused on two triple negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) to measure the effects of ALK4L75A-Fc on cancer cell behavior under nutrient deprivation and endoplasmic reticulum stress. We characterized the proliferation and migration of these cells in vitro using time-lapse microscopy and characterized stress-dependent changes in the levels and distribution of CRIPTO signaling mediators and cancer stem cell markers. We also assessed the effects of ALK4L75A-Fc on proliferation, EMT, and stem cell markers in vivo as well as on tumor growth and metastasis using inducible lentiviral delivery or systemic administration of purified ALK4L75A-Fc, which represents a candidate therapeutic approach. Results ALK4L75A-Fc inhibited adaptive responses of breast cancer cells under conditions of nutrient and ER stress and reduced their proliferation, migration, clonogenicity, and expression of EMT and cancer stem cell markers. ALK4L75A-Fc also inhibited proliferation of human breast cancer cells in stressed tumor microenvironments in xenografts and reduced both primary tumor size and metastatic burden. Conclusions Cancer cell adaptation to stresses such as nutrient deprivation, hypoxia, and chemotherapy can critically contribute to dormancy, metastasis, therapy resistance, and recurrence. Identifying mechanisms that govern cellular adaptation, plasticity, and the emergence of stem-like cancer cells may be key to effective anticancer therapies. Results presented here indicate that targeting CRIPTO with ALK4L75A-Fc may have potential as such a therapy since it inhibits breast cancer cell adaptation to microenvironmental challenges and associated stem-like and EMT phenotypes.

scholarly journals Cancer-Associated Fibroblasts Regulate the Plasticity of Breast Cancer Stemness through the Production of Leukemia Inhibitory Factor

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1298
Author(s):  
Nazanin Vaziri ◽  
Laleh Shariati ◽  
Ali Zarrabi ◽  
Ali Farazmand ◽  
Shaghayegh Haghjooy Javanmard
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Leukemia Inhibitory Factor ◽  
Breast Cancer Cells ◽  
Stem Cell Markers ◽  
Cancer Associated Fibroblasts ◽  
Cell Markers ◽  
Cancer Stem Cell Markers

Leukemia inhibitory factor (LIF), as a member of the interleukin-6 cytokine family, plays a complex role in solid tumors. However, the effect of LIF as a tumor microenvironment factor on plasticity control in breast cancer remains largely unknown. In this study, an in vitro investigation is conducted to determine the crosstalk between breast cancer cells and fibroblasts. Based on the results, cancer-associated fibroblasts are producers of LIF in the cocultivation system with breast cancer cells. Treatment with the CAF-CM and human LIF protein significantly promoted stemness through the dedifferentiation process and regaining of stem-cell-like properties. In addition, the results indicate that activation of LIFR signaling in breast cancer cells in the existence of CAF-secreted LIF can induce Nanog and Oct4 expression and increase breast cancer stem cell markers CD24−/CD44+. In contrast, suppression of the LIF receptor by human LIF receptor inhibition antibody decreased the cancer stem cell markers. We found that LIF was frequently overexpressed by CAFs and that LIF expression is necessary for dedifferentiation of breast cancer cell phenotype and regaining of cancer stem cell properties. Our results suggest that targeting LIF/LIFR signaling might be a potent therapeutic strategy for breast cancer and the prevention of tumor recurrence.

scholarly journals Differential effects of two HDAC inhibitors with distinct concomitant DNA hypermethylation or hypomethylation in breast cancer cells

2019 ◽  
Author(s):  
Arunasree M. Kalle ◽  
Zhibin Wang
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Cells ◽  
X Chromosome ◽  
Breast Cancer Cells ◽  
Trichostatin A ◽  
Methylation Status ◽  
Dna Methyltransferases ◽  
Dependent Manner ◽  
Dna Hypermethylation

AbstractDNA methylation and histone acetylation are the two important epigenetic phenomena that control the status of X-chromosome inactivation (XCI), a process of dosage compensation in mammals resulting in active X chromosome (Xa) and inactive X chromosome (Xi) in females. While DNA methyltransferases (DNMTs) are known to maintain the DNA hypermethylation of Xi, it remains to be determined how one or a few of 18 known histone deacetylases (HDACs) contribute(s) to Xi maintenance. Herein we found that HDAC1/2/4/6 were overexpressed in breast cancer cells, MDA-MB-231, with Xa/Xa status compared to normal breast epithelial cells, MCF10A, with Xa/Xi status. Inhibition of these overexpressed HDACs with two different drugs, sodium butyrate (SB) and Trichostatin A (TSA), caused surprisingly distinct effects on global DNA methylation: hypermethylation and hypomethylation, respectively, as well as distinct effects on a repressing histone mark H3K27me3 for heterochromatin and an active mark H3K56ac for DNA damage. Surveying three DNMTs through immunoblot analyses for insights revealed the up- or down-regulation of DNMT3A upon drug treatments in a concentration-dependent manner. These results correlated with the decreased XIST and increased TSIX expression in MDA-MB 231 as a possible mechanism of Xi loss and were reversed with SB treatment. Further RNA-seq analysis indicated differential gene expression correlating with the promoter methylation status of a few genes. Collectively, our results demonstrate a crosstalk between HDACs and DNMTs and the novel involvement of HDACs in skewed Xi in breast cancer.

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